Emily Tomasulo, Andy Itsara, Mark Haigney, Douglas R Rosing, Inhye E Ahn, Cody Peer, Beth A Kozel, Teresa Luperchio, Grace Ge, William D Figg, Adrian Wiestner, Clare Sun
{"title":"伊鲁替尼治疗慢性淋巴细胞白血病患者猝死和无症状心律失常。","authors":"Emily Tomasulo, Andy Itsara, Mark Haigney, Douglas R Rosing, Inhye E Ahn, Cody Peer, Beth A Kozel, Teresa Luperchio, Grace Ge, William D Figg, Adrian Wiestner, Clare Sun","doi":"10.1016/j.hrthm.2025.10.014","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ibrutinib (IBR) is a first-in-class Bruton's tyrosine kinase inhibitor (BTKi) approved in multiple hematologic conditions for indefinite use until disease progression or toxicity. Hypertension (HTN) and atrial fibrillation are well-recognized cardiac complications of BTKi; more recently, heart failure, additional arrhythmias, and sudden cardiac death (SCD) have been attributed to IBR. Next-generation covalent BTKi are also associated with cardiovascular complications, including SCD, albeit to a lesser degree.</p><p><strong>Objective: </strong>The incidence and clinical features of patients experiencing SCD and asymptomatic arrhythmias on IBR remain ill-defined. We aim to characterize the incidence of SCD and asymptomatic arrhythmias on IBR.</p><p><strong>Methods: </strong>We report: 1) a retrospective cohort analysis of 131 patients with a median of 66.5 months on IBR utilizing available cardiac testing, genetic sequencing, and autopsy review; 2) a cross-sectional cardiac analysis of 21 asymptomatic patients on IBR including ambulatory EKG, stress tests, and transthoracic echocardiograms.</p><p><strong>Results: </strong>The incidence of SCD in patients on IBR (n=5) was 801 per 100,000 patient-years, approximately 2-4x higher than the general population. All patients with SCD on IBR had at least one cardiac risk factor. Autopsies conducted in 3 of 5 patients with SCD did not reveal acute pathologic processes, but did demonstrate evolving cardiac pathology. Cardiovascular testing in asymptomatic patients on IBR revealed previously unknown clinically significant arrhythmias in 4 (19%) patients, leading to precautionary IBR discontinuation in 2 patients.</p><p><strong>Conclusion: </strong>IBR increases the risk of SCD among patients with cardiac risk factors. Stress and ambulatory EKG on IBR identified asymptomatic arrhythmias altering clinical management in 19% of patients. These data highlight the need for risk-mitigation strategies for patients starting or receiving IBR, and possibly extending to other BTKis.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sudden Death and Asymptomatic Arrhythmia in Chronic Lymphocytic Leukemia Patients Treated with Ibrutinib.\",\"authors\":\"Emily Tomasulo, Andy Itsara, Mark Haigney, Douglas R Rosing, Inhye E Ahn, Cody Peer, Beth A Kozel, Teresa Luperchio, Grace Ge, William D Figg, Adrian Wiestner, Clare Sun\",\"doi\":\"10.1016/j.hrthm.2025.10.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ibrutinib (IBR) is a first-in-class Bruton's tyrosine kinase inhibitor (BTKi) approved in multiple hematologic conditions for indefinite use until disease progression or toxicity. Hypertension (HTN) and atrial fibrillation are well-recognized cardiac complications of BTKi; more recently, heart failure, additional arrhythmias, and sudden cardiac death (SCD) have been attributed to IBR. Next-generation covalent BTKi are also associated with cardiovascular complications, including SCD, albeit to a lesser degree.</p><p><strong>Objective: </strong>The incidence and clinical features of patients experiencing SCD and asymptomatic arrhythmias on IBR remain ill-defined. We aim to characterize the incidence of SCD and asymptomatic arrhythmias on IBR.</p><p><strong>Methods: </strong>We report: 1) a retrospective cohort analysis of 131 patients with a median of 66.5 months on IBR utilizing available cardiac testing, genetic sequencing, and autopsy review; 2) a cross-sectional cardiac analysis of 21 asymptomatic patients on IBR including ambulatory EKG, stress tests, and transthoracic echocardiograms.</p><p><strong>Results: </strong>The incidence of SCD in patients on IBR (n=5) was 801 per 100,000 patient-years, approximately 2-4x higher than the general population. All patients with SCD on IBR had at least one cardiac risk factor. Autopsies conducted in 3 of 5 patients with SCD did not reveal acute pathologic processes, but did demonstrate evolving cardiac pathology. Cardiovascular testing in asymptomatic patients on IBR revealed previously unknown clinically significant arrhythmias in 4 (19%) patients, leading to precautionary IBR discontinuation in 2 patients.</p><p><strong>Conclusion: </strong>IBR increases the risk of SCD among patients with cardiac risk factors. Stress and ambulatory EKG on IBR identified asymptomatic arrhythmias altering clinical management in 19% of patients. These data highlight the need for risk-mitigation strategies for patients starting or receiving IBR, and possibly extending to other BTKis.</p>\",\"PeriodicalId\":12886,\"journal\":{\"name\":\"Heart rhythm\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Heart rhythm\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.hrthm.2025.10.014\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heart rhythm","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.hrthm.2025.10.014","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Sudden Death and Asymptomatic Arrhythmia in Chronic Lymphocytic Leukemia Patients Treated with Ibrutinib.
Background: Ibrutinib (IBR) is a first-in-class Bruton's tyrosine kinase inhibitor (BTKi) approved in multiple hematologic conditions for indefinite use until disease progression or toxicity. Hypertension (HTN) and atrial fibrillation are well-recognized cardiac complications of BTKi; more recently, heart failure, additional arrhythmias, and sudden cardiac death (SCD) have been attributed to IBR. Next-generation covalent BTKi are also associated with cardiovascular complications, including SCD, albeit to a lesser degree.
Objective: The incidence and clinical features of patients experiencing SCD and asymptomatic arrhythmias on IBR remain ill-defined. We aim to characterize the incidence of SCD and asymptomatic arrhythmias on IBR.
Methods: We report: 1) a retrospective cohort analysis of 131 patients with a median of 66.5 months on IBR utilizing available cardiac testing, genetic sequencing, and autopsy review; 2) a cross-sectional cardiac analysis of 21 asymptomatic patients on IBR including ambulatory EKG, stress tests, and transthoracic echocardiograms.
Results: The incidence of SCD in patients on IBR (n=5) was 801 per 100,000 patient-years, approximately 2-4x higher than the general population. All patients with SCD on IBR had at least one cardiac risk factor. Autopsies conducted in 3 of 5 patients with SCD did not reveal acute pathologic processes, but did demonstrate evolving cardiac pathology. Cardiovascular testing in asymptomatic patients on IBR revealed previously unknown clinically significant arrhythmias in 4 (19%) patients, leading to precautionary IBR discontinuation in 2 patients.
Conclusion: IBR increases the risk of SCD among patients with cardiac risk factors. Stress and ambulatory EKG on IBR identified asymptomatic arrhythmias altering clinical management in 19% of patients. These data highlight the need for risk-mitigation strategies for patients starting or receiving IBR, and possibly extending to other BTKis.
期刊介绍：
HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability.
HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community.
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.
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